This ShEEP request is for a Vevo 3100 rodent imaging system to support the success and growth of multi- disciplinary research programs led by numerous VA-funded Principal Investigators at the San Francisco VA Medical Center. The current instrument available for cardiac imaging at our medical center is of low resolution and cannot provide 4-dimentional assessments of cardiac function, nor can it support high-resolution studies of cardiac wall geometry, stiffness and remodeling in response to volume overload or ischemia. Features only available on the Vevo 3100 will provide users with accurate kinetic and volumetric data for all 4 chambers of the heart, as well as large vessels for studies of atherosclerosis and aortic aneurysm biology. The system will be ideal to foster the success of numerous VA-funded projects that focus on developing new drugs to treat heart failure and vascular diseases that are significant clinical problems among the Veterans. The versatility of the Vevo 3100 will also lend itself of great value for the study of other disease models including liver and kidney cirrhosis, as well a variety of abdominal oncology models that cannot at this time be supported with existing instrumentation available to us. The Vevo 3100 will add tremendously to Dr. Raffai’s VA-funded research program that studies extracellular vesicles, including exosomes in modulating inflammation in atherosclerosis cardiovascular disease. The Vevo 3100 will provide a new dimension to test anti-inflammatory exosome-based biologics in controlling atherosclerotic lesion burden and aneurysms in the aorta, and in preventing cardiac dysfunction and heart failure in mice that survive myocardial infarctions. Furthermore, the ability to measure liver stiffness will allow for collaborative studies of liver cirrhosis with Dr. Willenbring at UCSF as a minor non-VA user. Similarly, the system will be of great value to Dr. Baker’s VA-funded program that investigates heart failure involving the cardiac right ventricle (RV) and develop new drugs for its treatment. RV failure is a serious and common disease that predisposes to death in patients with pulmonary hypertension including among Veterans. The small size of the RV cannot be imaged with the current echo system but will be available via the Vevo 3100. Drs. Simpson is a VA-funded cardiologist who works on developing new drugs for HFpEF where diastolic dysfunction is predominant and represent 50% of all cases of heart failure. The current echocardiographic system available to him is inadequate to support these studies and only the Vevo 3100 will solve the problem of quantifying two key indices in HFpEF, namely diastolic function and ventricular strain. Dr. Lau studies sex differences in human cardiovascular disease and liver cancer. He is VA-funded to study male-specific genes and sex hormone/receptors in non-alcoholic fatty liver disease and liver cancer. He now also studies sex differences in pulmonary arterial hypertension ...